tbuckley/cabot-search huggingface dataset:
Classification of the tumor immune microenvironment and associations with outcomes in patients with metastatic melanoma treated with immunotherapies
Authors: Nurudeen A Adegoke, Tuba N Gide, Yizhe Mao, Camelia Quek, Ellis Patrick, Matteo S Carlino, Serigne N Lo, Alexander Maxwell Menzies, Ines Pires da Silva, Ismael A Vergara, Georgina Long, Richard A Scolyer, James S Wilmott
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Tumor microenvironment (TME) characteristics are potential biomarkers of response to immune checkpoint inhibitors in metastatic melanoma. This study developed a method to perform unsupervised classification of TME of metastatic melanoma. Methods We used multiplex immunohistochemical and quantitative pathology-derived assessment of immune cell compositions of intratumoral and peritumoral regions of metastatic melanoma baseline biopsies to classify TME in relation to response to anti-programmed cell death protein 1 (PD-1) monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4 (ipilimumab (IPI)+PD-1). Results Spatial profiling of CD8+T cells, macrophages, and melanoma cells, as well as phenotypic PD-1 receptor ligand (PD-L1) and CD16 proportions, were used to identify and classify patients into one of three mutually exclusive TME classes: immune-scarce, immune-intermediate, and immune-rich tumors. Patients with immune-rich tumors were characterized by a lower proportion of melanoma cells and higher proportions of immune cells, including higher PD-L1 expression. These patients had higher response rates and longer progression-free survival (PFS) than those with immune-intermediate and immune-scarce tumors. At a median follow-up of 18 months (95% CI: 6.7 to 49 months), the 1-year PFS was 76% (95% CI: 64% to 90%) for patients with an immune-rich tumor, 56% (95% CI: 44% to 72%) for those with an immune-intermediate tumor, and 33% (95% CI: 23% to 47%) for patients with an immune-scarce tumor. A higher response rate was observed in patients with an immune-scarce or immune-intermediate tumor when treated with IPI+PD-1 compared with those treated with PD-1 alone. Conclusions Our study provides an automatic TME classification method that may predict the clinical efficacy of immunotherapy for patients with metastatic melanoma.
1215P Comparative analysis of cfDNA liquid biopsy and tumor-based next-generation sequencing (NGS) approaches
Authors: A. Yudina, S. Starikov, A. Efremov, D. Sookiasian, E. Nuzhdina, S. Podsvirova, M. Chasse, T. Conroy, N. English, A. Love, D. Tabakov, A. Baisangurov, C. Tazearslan, N. Fowler, A. Bagaev
Journal: Annals of Oncology (2023)
1209MO Computer-aided HCC lesion detection based on deep learning and CT images
Authors: O. Lucidarme, T. Broussaud, S. Bodard, V. Paradis, I. Brocheriou, C. Guettier, L. Ayache, C. Bougharka, A. O'Keane, S. Poullot, J. Shen, V.K. Le, E. Geremia, V. Groza, Q. Renault, M. Macrez, T. Foriel, Y. Liu, M. Lewin-Zeitoun, V. Vilgrain
Journal: Annals of Oncology (2023)
1208MO A randomized phase III trial of site-specific therapy guided by the 90-gene expression assay versus empiric chemotherapy in patients with cancer of unknown primary
Authors: Z. Luo, X. Liu, X. Zhang, S. Jiang, M. Mo, Q. Wang, Y. Wang, L. Zhou, S. Hu, H. Yang, Y. Hou, Y. Chen, X. Lu, X. Zhou, W. Li, X. Yang, K. Chen, J. Cao, Q. Xu, X. Hu
Journal: Annals of Oncology (2023)
Challenges in adult services for a young adult with a rare skin disease
Authors: Maddie Valleekanthan, Hannah Cree
Journal: British Journal of Dermatology (2023)

Maddie, a 17-year-old patient with congenital melanocytic naevi who is a Young Ambassador with Caring Matters Now, wrote this article while on work experience with the Support Pathway Practitioner for the charity. This article discusses how young adult members should be supported while transitioning to adult services and the challenges faced by young people affected by a rare skin disease as they transition from specialized care to local services.
Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis
Authors: Ross A. Soo, Byoung Chul Cho, Joo-Hang Kim, Myung-Ju Ahn, Ki Hyeong Lee, Anastasia Zimina, Sergey Orlov, Igor Bondarenko, Yun-Gyoo Lee, Yueh Ni Lim, Sung Sook Lee, Kyung-Hee Lee, Yong Kek Pang, Chin Heng Fong, Jin Hyoung Kang, Chun Sen Lim, Pongwut Danchaivijitr, Saadettin Kilickap, James Chih-Hsin Yang, Cagatay Arslan, Hana Lee, Seong Nam Park, Irfan Cicin
Journal: Journal of Thoracic Oncology (2023)

IntroductionLazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases.MethodsTreatment-naive patients with EGFR–mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.ResultsOf the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8–28.2) versus 8.4 months (95% CI: 6.7–not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20–0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3–NR) versus 6.3 months (2.8–NR) with gefitinib. Tolerability was similar to the overall LASER301 population.ConclusionsIn patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.
Mental health outcomes in a population-based cohort of patients with prostate cancer
Authors: Siqi Hu, Chun-Pin Chang, John Snyder, Vikrant Deshmukh, Michael Newman, Ankita Date, Carlos Galvao, Benjamin Haaland, Christina A Porucznik, Lisa H Gren, Alejandro Sanchez, Shane Lloyd, Brock O’Neil, Mia Hashibe
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Few studies have evaluated mental health disorders comprehensively among patients with prostate cancer on long-term follow-up. The primary aim of our study was to assess the incidence of mental health disorders among patients with prostate cancer compared with a general population cohort. A secondary aim was to investigate potential risk factors for mental health disorders among patients with prostate cancer. Methods Cohorts of 18 134 patients with prostate adenocarcinomas diagnosed between 2004 and 2017 and 73470 men without cancer matched on age, birth state, and follow-up time were identified. Mental health diagnoses were identified from electronic health records and statewide health-care facilities data. Cox proportional hazard models were used to estimate hazard ratios. All statistical tests were 2-sided. Results The hazard ratios for mood disorders, including depression, among prostate cancer survivors increased for all follow-up periods compared with the general population. The hazard ratios for any mental illness increased with Hispanic, Black, or multiple races; people who were underweight or obese; those with advanced prostate cancer; and those undergoing their first course cancer treatment. We also observed statistically significantly increased hazard ratios for mental health disorders among patients with lower socioeconomic status (P &amp;lt; .0001) and increasing duration of androgen-deprivation therapy (P = .0348). Prostate cancer survivors had a 61% increased hazard ratio for death with a depression diagnosis. Conclusion Prostate cancer diagnosis was associated with a higher risk of mental health disorders compared with the general population, which was observed as long as 10-16 years after cancer diagnosis. Providing long-term mental health support may be beneficial to increasing life expectancy for patients with prostate cancer.
Magnesium sulphate in patients with thrombotic thrombocytopenic purpura (MAGMAT): a randomised, double-blind, superiority trial
Authors: Lara Zafrani, Emmanuel Canet, Anouk Walter-Petrich, Bérangère Joly-Laffargue, Agnès Veyradier, Stanislas Faguer, Naïke Bigé, Laure Calvet, Julien Mayaux, Steven Grangé, Cédric Rafat, Coralie Poulain, Kada Klouche, Pierre Perez, Frédéric Pène, Claire Pichereau, Baptiste Duceau, Eric Mariotte, Sylvie Chevret, Elie Azoulay
Journal: Intensive Care Medicine (2023)
Calcium-based biomaterials: Unveiling features and expanding applications in osteosarcoma treatment
Authors: Yilun Wu, Min Cheng, Yi Jiang, Xin Zhang, Jiaxiang Li, Yishen Zhu, Qingqiang Yao
Journal: Bioactive Materials (2023)

Calcium, an indispensable element in bone tissues, plays a crucial role in various cellular processes involved in cancer progression. Its ubiquitous yet spatially distinct distribution in the body presents an opportunity to target calcium homeostasis as a novel strategies for cancer treatment, with specific advantages in osteosarcoma therapy. In this comprehensive review, we retrospect the calcium biology intersected with cancer progression, highlight the unveiling features of calcium-based biomaterials in regulating both bone homeostasis and cancer development. We also provide an overview of recent breakthroughs in cancer therapy that leverage calcium biomaterials, showcasing their potential to serve as versatile, customizable platforms for osteosarcoma treatment and as reservoirs for supporting bone reconstruction.
Nivolumab plus Gemcitabine–Cisplatin in Advanced Urothelial Carcinoma
Authors: Michiel S van der Heijden, Guru Sonpavde, Thomas Powles, Andrea Necchi, Mauricio Burotto, Michael Schenker, Juan Pablo Sade, Aristotelis Bamias, Philippe Beuzeboc, Jens Bedke, Jan Oldenburg, Gurkamal Chatta, Yüksel Ürün, Dingwei Ye, Zhisong He, Begoña P Valderrama, Ja Hyeon Ku, Yoshihiko Tomita, Jeiry Filian, Lily Wang, Daniela Purcea, Miraj Y Patel, Federico Nasroulah, Matthew D Galsky
Journal: New England Journal of Medicine (2023)

No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy.In this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes.A total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P = 0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P = 0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine-cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively.Combination therapy with nivolumab plus gemcitabine-cisplatin resulted in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma than gemcitabine-cisplatin alone. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 901 ClinicalTrials.gov number, NCT03036098.).
Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated <i>KRAS</i> G12C
Authors: Marwan G. Fakih, Lisa Salvatore, Taito Esaki, Dominik P. Modest, David P. Lopez-Bravo, Julien Taieb, Michalis V. Karamouzis, Erika Ruiz-Garcia, Tae-Won Kim, Yasutoshi Kuboki, Fausto Meriggi, David Cunningham, Kun-Huei Yeh, Emily Chan, Joseph Chao, Yaneth Saportas, Qui Tran, Chiara Cremolini, Filippo Pietrantonio
Journal: New England Journal of Medicine (2023)

G12C is a mutation that occurs in approximately 3 to 4% of patients with metastatic colorectal cancer. Monotherapy with KRAS G12C inhibitors has yielded only modest efficacy. Combining the KRAS G12C inhibitor sotorasib with panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, may be an effective strategy.
Blood brain barrier-targeted delivery of double selenium nanospheres ameliorates neural ferroptosis in Alzheimer's disease
Authors: Jingyuan Wang, Zekun Wang, Yuqing Li, Yajun Hou, Chenyang Yin, Endong Yang, Ziyu Liao, Cundong Fan, Lisandra L. Martin, Dongdong Sun
Journal: Biomaterials (2023)

Alzheimer's disease (AD) as a common neurodegenerative disease showed progressive cognitive dysfunction and behavioral impairment. Currently, the deposition of amyloid β-protein (Aβ) remains the main pathomechanism. However, preventing neuronal death induced by Aβ remains elusive, and no effective strategy in clinic was found to combat AD. Herein, a multifunctional double selenium nanosphere (CLNDSe) was designed and prepared, and A
Systemic allergic contact dermatitis to palladium, platinum, and titanium: mechanisms, clinical manifestations, prevalence, and therapeutic approaches
Authors: Ali Sadrolvaezin, Arezou Pezhman, Iman Zare, Shima Zahed Nasab, Sajad Chamani, Ali Naghizadeh, Ebrahim Mostafavi
Journal: MedComm (2023)

Abstract Contact dermatitis (CD) is an inflammatory skin disease of eczema that is elicited by chemicals or metal ions that have toxic effects without eliciting a T‐cell response (contact elicitation) or by small reactive chemicals that modify proteins and induce innate and adaptive immune responses (contact allergens). The clinical condition is characterized by localized skin rash, pruritus, redness, swelling, and lesions, which are mainly detected by patch tests and lymphocyte stimulation. Heavy metals such as palladium (Pd), platinum (Pt), and titanium (Ti) are ubiquitous in our environment. These heavy metals have shown CD effects as allergic agents. Immunological responses result from the interaction of cytokines and T cells. Occupational metal CD accounts for most cases of work‐related cutaneous disorders. In this systematic review, the allergic effects of heavy metals, including Pd, Pt, and Ti, and the mechanisms, clinical manifestations, prevalence, and therapeutic approaches are discussed in detail. Furthermore, the therapeutic approaches introduced to treat CD, including corticosteroids, topical calcineurin inhibitors, systemic immunosuppressive agents, phototherapy, and antihistamines, can be effective in the treatment of these diseases in the future. Ultimately, the insights identified could lead to improved therapeutic and diagnostic pathways.
Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance
Authors: Huize Shen, Rui Zhu, Yanyang Liu, Yangjian Hong, Jiaming Ge, Jie Xuan, Wenyuan Niu, Xuefei Yu, Jiang-Jiang Qin, Qinglin Li
Journal: Drug Resistance Updates (2023)

Radioiodine refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter (NIS) in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multi-kinase inhibitors (MKIs) and other chemicals and restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review article, we summarized the major gene mutation, gene rearrangement, and abnormal expression of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the agents that have been tested in clinical and preclinical trials.
The impact of genomic context on outcomes of solid cancer patients treated with genotype-matched targeted therapies: a comprehensive review
Authors: T. Fulton-Ward, G. Middleton
Journal: Annals of Oncology (2023)

Background A critical need in the field of genotype-matched targeted therapy in cancer is to identify patients unlikely to respond to precision medicines. This will manage expectations of individualised therapies and avoid clinical progression to a point where institution of alternative treatments might not be possible. We examined the evidence base of the impact of genomic context on which targeted alterations are inscribed to identify baseline biomarkers distinguishing those obtaining the expected response from those with less benefit from targeted therapies. Methods A comprehensive narrative review was conducted: scoping searches were undertaken in PubMed, Cochrane Database of Systematic Reviews, and PROSPERO. Outcomes included in meta-analysis were progression-free and overall survival. Data was extracted from Kaplan-Meier and used to calculate hazard ratios. Studies presenting data on two molecular sub-cohorts (e.g., co-mutation vs no co-mutation) were included in fixed meta-analysis. Other studies were used for descriptive purposes. Results The presence of concomitant driver mutations, higher tumour mutational burden(TMB), greater copy number burden and APOBEC signatures significantly reduces benefits of targeted therapy in lung cancers in never smokers(LCINS) and breast cancer; cancers with low TMB. LCINS have significantly poorer outcomes if their cancers harbour p53 co-mutations, an effect also seen in HER2+ breast cancer patients (trastuzumab) and head and neck cancer (PI3K inhibition). PI3K co-alterations have less impact when targeting EGFR-mutations and ALK-fusions, but significantly reduce the impact of targeting HER2- and MET-amplifications. SMARCA4 co-mutations predict for poor outcome in patients treated with osimertinib and sotorasib. In BRAF-mutant melanoma, whilst there are no genomic features distinguishing exceptional responders from primary progressors, there are clear transcriptomic features dichotomising these outcomes. Conclusion To our knowledge this is the most comprehensive review to date of the impact of genomic context on outcomes with targeted therapy. It represents a valuable resource informing progress towards contextualised precision medicine.
An urgent call to save and protect lives of vulnerable populations in the Gaza Strip
Authors: Abdallah Abudayya, Khaled Abu Ghali, Sally Hargreaves, Karl Blanchet, Espen Bjertness, Anand S. Bhopal, Charles Agyemang, Gerd Holmboe-Ottersen, Raj S. Bhopal, Allan Krasnik, Sonia Dias, Lars Lien, Anuj Kapilashrami, Bernadette N. Kumar
Journal: The Lancet Regional Health - Europe (2023)
Embedded 3D bioprinting – An emerging strategy to fabricate biomimetic &amp; large vascularized tissue constructs
Authors: Harshavardhan Budharaju, Dhakshinamoorthy Sundaramurthi, Swaminathan Sethuraman
Journal: Bioactive Materials (2023)

Three-dimensional bioprinting is an advanced tissue fabrication technique that allows printing complex structures with precise positioning of multiple cell types layer-by-layer. Compared to other bioprinting methods, extrusion bioprinting has several advantages to print large-sized tissue constructs and complex organ models due to large build volume. Extrusion bioprinting using sacrificial, support and embedded strategies have been successfully employed to facilitate printing of complex and hollow structures. Embedded bioprinting is a gel-in-gel approach developed to overcome the gravitational and overhanging limits of bioprinting to print large-sized constructs with a micron-scale resolution. In embedded bioprinting, deposition of bioinks into the microgel or granular support bath will be facilitated by the sol-gel transition of the support bath through needle movement inside the granular medium. This review outlines various embedded bioprinting strategies and the polymers used in the embedded systems with advantages, limitations, and efficacy in the fabrication of complex vascularized tissues or organ models with micron-scale resolution. Further, the essential requirements of support bath systems like viscoelasticity, stability, transparency and easy extraction to print human scale organs are discussed. Additionally, the organs or complex geometries like vascular constructs, heart, bone, octopus and jellyfish models printed using support bath assisted printing methods with their anatomical features are elaborated. Finally, the challenges in clinical translation and the future scope of these embedded bioprinting models to replace the native organs are envisaged.
Thinking Differently—On Solitude and Productivism
Authors: Colin Sue-Chue-Lam
Journal: JAMA Internal Medicine (2023)

To the Editor Taran1 asks us to see Rodin’s The Thinker as a reminder to clinicians to take the time to think deeply about their careers. This is an important provocation for what it says about how thinking ought to look, and how we ought to spend our time alone.
Safety and Benefits of COVID-19 Vaccination in Pregnancy—Implications for the Maternal Vaccination Platform
Authors: Catherine Mary Healy, Laura E. Riley
Journal: JAMA Pediatrics (2023)

Sarah C. J. Jorgensen, PharmD, MPH; Samantha S. M. Drover, PhD; Deshayne B. Fell, PhD; Peter C. Austin, PhD; Rohan D'Souza, MD, PhD; Astrid Guttmann, MDCM, MSc; Sarah A. Buchan, PhD; Sarah E. Wilson, MD; Sharifa Nasreen, PhD; Kevin L. Schwartz, MD, MSc; Mina Tadrous, PharmD, PhD; Kumanan Wilson, MD, MSc; Jeffrey C. Kwong, MD, MSc